Gemcitabine Hydrochloride and Alvocidib in Treating Patients With Solid Tumors

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This phase I trial is studying the side effects and best dose of gemcitabine hydrochloride and alvocidib in treating patients with solid tumors. Drugs used in chemotherapy, such as gemcitabine hydrochloride and alvocidib, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

I. Determine the maximum tolerated dose of gemcitabine and flavopiridol in patients with solid tumors.

SECONDARY OBJECTIVES:

I. Determine the safety profile and toxic effects of this regimen in these patients.

II. Determine the pharmacokinetics of flavopiridol with and without gemcitabine in these patients.

III. Determine, using pharmacodynamic assays, the activity of flavopiridol as a cdk inhibitor in these patients.

IV. Determine, using pharmacodynamic assays, the markers of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and alvocidib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.

Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and alvocidib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Negative pregnancy test

Fertile patients must use effective contraception

No active infection

No severe malnutrition

No more than 2 prior chemotherapy regimens:

Prior combined modality therapy (e.g., full-dose chemotherapy with radiosensitizing chemotherapy and radiotherapy) is considered 1 prior regimen if all therapy was delivered as part of 1 comprehensive treatment plan

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

No other concurrent chemotherapy

At least 6 months since prior radiotherapy to the lung parenchyma or mediastinum and no evidence of radiation pneumonitis on chest CT scan

At least 4 weeks since other prior radiotherapy and recovered

No prior radiotherapy to more than 50% of marrow volume

No concurrent radiotherapy

Histologically confirmed solid tumor for which gemcitabine is a treatment option OR for which no efficacious therapy exists